Multiple expression forms of the hS0S1 and GRF genes were detected in polyA+ mRNA Northerns from human adult and fetal tissues, including brain. placenta. pancreas. lung. kidney and skeletal muscle. Consistent with this variety of mRNA transcripts, in soluble fraction (5100) and in membrane (P100) of different human tissues, several protein forms that were recognized specifically in Western immunoblots were detected. In both cases transcripts and protein bands that are common to all the tissues tested were found, while others are expressed in a tissue- specific manner. In this same line, a 45 nucleotide insertion in Sos mRNA from skeletal muscle, which is absent in Sos mRNA from fetal brain, was detected. This insertion is also present in other tissues, both in fetal and adult. All of these findings suggest that both SOS and GRF gene products suffer alternative splicing and that the multiple forms originated may contribute to the fine regulation of guanine exchange factors (GEF) activity in different tissues or at different stages of development.